This project has to do with a series of drugs called carbonic anhydrase inhibitors, which affect many secretory or fluid producing systems in the body. As a result, their use has been beneficial in several diseases, including glaucoma, congestive heart failure, hydrocephalus and periodic paralysis. The studies described here are attempts to more thoroughly understand the mechanisms behind these curative effects, and also to extend them. We use experimental animals, and also patients that are being treated with these drugs. The range of information produced is from the chemical to the physiological to the clinical, and attempts are continuously made to integrate these. The proposed work will measure the rates at which various ions enter muscle, cerebrospinal fluid, and other body fluids under the influence of carbonic anhydrase. We seek specifically to find the mechanism by which secretory cells separate charge, leading to secretion of H positive and OH negative. These in vivo experiments will be backed up by chemical exploration of the carbonic anhydrase system, and ion exchange in isolated cells.